ADA formation with once-weekly insulin efsitora did not significantly impact its efficacy or safety profile. A pooled evaluation from five phase 3 trials, published in Diabetes, Obesity and Metabolism, assessed immunogenicity outcomes in participants with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus 

(T2DM).Serum samples collected at baseline and throughout treatment were analyzed for ADA formation, cross-reactivity with native insulin, and neutralizing activity against efsitora or endogenous insulin. Pharmacokinetics were evaluated using efsitora clearance. Glycemic efficacy was measured by glycated hemoglobin (HbA1c) change from baseline at the primary endpoint. Safety analyses included hypersensitivity and injection-site reactions by ADA status.

Treatment-emergent ADA developed in 0.6% of 341 participants with T1DM and 3.0% of 1861 participants with T2DM. In T2DM, cross-reactivity to native insulin was detected in 1.7%, and neutralizing activity against efsitora or native insulin occurred in 1.1% and 0.8%. Maximum ADA titers ranged from 1:40 to 1:81 920 (median 1:80). Efsitora clearance, HbA1c outcomes, and safety events showed no meaningful differences between ADA-positive and ADA-negative individuals.

These findings demonstrate that insulin efsitora exhibits low immunogenicity, with no observable effect on clinical performance across diabetes populations evaluated.